Vaccines are effective tools to reduce diseases but often target only a subset of strains causing illness, allowing the emergence of vaccine evasion. Genomics has become a key tool for pathogen surveillance. Here we present insights gained from the Global Pneumococcal Sequencing project (2011–present), highlighting recent advancements in genome-based tools that provide valuable information for monitoring strain evolution and guiding vaccine design.
Since the introduction of pneumococcal conjugate vaccine (PCV) in 2000, we analyzed >40,000 pneumococcal genomes from >60 countries. New tools were created to capture variations across the entire genome, enabling identification of 1,053 pneumococcal lineages and accurate prediction of susceptibility to 20 antibiotics, inferring 102 out of 107 known vaccine antigens (i.e., serotypes), identifying novel serotypes, and assessing distribution of protein antigens.
The analysis identified only 35 lineages that are globally disseminated. Several lineages were predisposed to vaccine evasion by producing diverse serotypes prior to PCV introduction. Lineage GPSC10 alone can produce 17 serotypes, allowing escape from PCV7 via serotype 19A and PCV13 via serotype 24F. These findings played a role in the decision to include serotype 24F in the upcoming 25-valent PCV (IVT-25) and also highlights limitations of a serotype-based vaccine approach. Additionally, we identified three novel serotypes, one of which (33E) has high potential to evade PCV15/PCV20. We estimated theoretical vaccine coverage of serotypes by evaluating the prevalence of potential protein antigens in the global collection.
This project demonstrates how genomic surveillance deciphers mechanisms of vaccine evasion, offering valuable insights for future vaccine development.